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Ageno W.,University of Insubria | Riva N.,University of Insubria | Schulman S.,McMaster University | Beyer-Westendorf J.,University Hospital Carl Gustav Carus | And 22 more authors.
JAMA Internal Medicine

IMPORTANCE: Little information is available on the long-term clinical outcome of patients with splanchnic vein thrombosis (SVT). OBJECTIVE: To assess the incidence rates of bleeding, thrombotic events, and mortality in a large international cohort of patients with SVT. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted beginning May 2,2008, and completed January 30,2014, at hospital-based centers specialized in the management of thromboembolic disorders; a 2-year follow-up period was completed January 30, 2014, and data analysis was conducted from July 1, 2014, to February 28, 2015. Participants included 604 consecutive patients with objectively diagnosed SVT; there were no exclusion critieria. Information was gathered on baseline characteristics, risk factors, and antithrombotic treatment. Clinical outcomes during the follow-up period were documented and reviewed by a central adjudication committee. MAIN OUTCOMES AND MEASURES: Major bleeding, defined according to the International Society on Thrombosis and Hemostasis; bleeding requiring hospitalization; thrombotic events, including venous and arterial thrombosis; and all-cause mortality. RESULTS: Of the 604 patients (median age, 54 years; 62.6% males), 21 (3.5%) did not complete follow-up. The most common risk factors for SVT were liver cirrhosis (167 of 600 patients [27.8%]) and solid cancer (136 of 600 [22.7%]); the most common sites of thrombosis were the portal vein (465 of 604 [77.0%]) and the mesenteric veins (266 of 604 [44.0%]). Anticoagulation was administered to 465 patients in the entire cohort (77.0%) with a mean duration of 13.9 months; 175 of the anticoagulant group (37.6%) received parenteral treatment only, and 290 patients (62.4%) were receiving vitamin K antagonists. The incidence rates (reported with 95% CIs) were 3.8 per 100 patient-years (2.7-5.2) for major bleeding, 7.3 per 100 patient-years (5.8-9.3) for thrombotic events, and 10.3 per 100 patient-years (8.5-12.5) for all-cause mortality. During anticoagulant treatment, these rates were 3.9 per 100 patient-years (2.6-6.0) for major bleeding and 5.6 per 100 patient-years (3.9-8.0) for thrombotic events. After treatment discontinuation, rates were 1.0 per 100 patient-years (0.3-4.2) and 10.5 per 100 patient-years (6.8-16.3), respectively. The highest rates of major bleeding and thrombotic events during the whole study period were observed in patients with cirrhosis (10.0 per 100 patient-years [6.6-15.1] and 11.3 per 100 patient-years [7.7-16.8], respectively); the lowest rates were in patients with SVT secondary to transient risk factors (0.5 per 100 patient-years [0.1-3.7] and 3.2 per 100 patient-years [1.4-7.0], respectively). CONCLUSIONS AND RELEVANCE: Most patients with SVT have a substantial long-term risk of thrombotic events. In patients with cirrhosis, this risk must be balanced against a similarly high risk of major bleeding. Anticoagulant treatment appears to be safe and effective in most patients with SVT. Copyright 2015 American Medical Association. All rights reserved. Source

Patnaik M.M.,Mayo Medical School | Lasho T.L.,Mayo Medical School | Finke C.M.,Mayo Medical School | Gangat N.,Mayo Medical School | And 9 more authors.

The 2008 World Health Organization (WHO) criteria were used to identify 88 consecutive Mayo Clinic patients with myelodysplastic syndrome with isolated del(5q) (median age 74 years; 60 females). In all, 60 (68%) patients were followed up to the time of their death. Overall median survival was 66 months; leukemic transformation was documented in five (5.7%) cases. Multivariable analysis identified age 70 years (P0.01), transfusion need at diagnosis (P0.04) and dysgranulopoiesis (P0.02) as independent predictors of shortened survival; the presence of zero (low risk), one (intermediate risk) or 2 (high risk) risk factors corresponded to median survivals of 102, 52 and 27 months, respectively. Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), isocitrate dehydrogenase 1 (IDH1) and IDH2 mutational analysis was performed on archived bone marrows in 78 patients; JAK2V617F and MPLW515L mutations were shown in five (6.4%) and three (3.8%) patients, respectively, and did not seem to affect phenotype or prognosis. IDH mutations were not detected. Survival was not affected by serum ferritin and there were no instances of death directly related to iron overload. The current study is unique in its strict adherence to WHO criteria for selecting study patients and providing information on long-term survival, practical prognostic factors, baseline risk of leukemic transformation and the prevalence of JAK2, MPL and IDH mutations. © 2010 Macmillan Publishers Limited All rights reserved. Source

Tefferi A.,Mayo Medical School | Lasho T.L.,Mayo Medical School | Abdel-Wahab O.,Sloan Kettering Cancer Center | Guglielmelli P.,University of Florence | And 12 more authors.

In a multi-institutional collaborative project, 1473 patients with myeloproliferative neoplasms (MPN) were screened for isocitrate dehydrogenase 1 (IDH1)/IDH2 mutations: 594 essential thrombocythemia (ET), 421 polycythemia vera (PV), 312 primary myelofibrosis (PMF), 95 post-PV/ET MF and 51 blast-phase MPN. A total of 38 IDH mutations (18 IDH1-R132, 19 IDH2-R140 and 1 IDH2-R172) were detected: 5 (0.8%) ET, 8 (1.9%) PV, 13 (4.2%) PMF, 1 (1%) post-PV/ET MF and 11 (21.6%) blast-phase MPN (P0.01). Mutant IDH was documented in the presence or absence of JAK2, MPL and TET2 mutations, with similar mutational frequencies. However, IDH-mutated patients were more likely to be nullizygous for JAK2 46/1 haplotype, especially in PMF (P0.04), and less likely to display complex karyotype, in blast-phase disease (P0.01). In chronic-phase PMF, JAK2 46/1 haplotype nullizygosity (P0.01; hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7-5.2), but not IDH mutational status (P0.55; HR 1.3, 95% CI 0.5-3.4), had an adverse effect on survival. This was confirmed by multivariable analysis. In contrast, in both blast-phase PMF (P0.04) and blast-phase MPN (P0.01), the presence of an IDH mutation predicted worse survival. The current study clarifies disease- and stage-specific IDH mutation incidence and prognostic relevance in MPN and provides additional evidence for the biological effect of distinct JAK2 haplotypes. © 2010 Macmillan Publishers Limited All rights reserved. Source

Tefferi A.,Mayo Medical School | Siragusa S.,Policlinico Universitario Of Palermo | Hussein K.,Mayo Medical School | Schwager S.M.,Mayo Medical School | And 4 more authors.
American Journal of Hematology

The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty-two patients (∼24%) required transfusions at diagnosis whereas 22 (∼9%) became transfusion-dependent and 170 remained transfusion-independent during the first year postdiagnosis; after a median follow-up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS- and karyotypeindependent prognostic weight of transfusion status. Among IPSS intermediate-1 risk patients, overall median survival of 82 months was modified to 60 or 118 months, based on presence or absence of transfusion need, respectively (P < 0.01). The corresponding figures for intermediate-2/high risk patients were 30 and 64 months (P < 0.01). Documented causes of death did not include iron overload. We conclude that transfusion status in PMF downgrades or upgrades prognosis within specific IPSS categories; transfusion need is a marker of aggressive disease biology in PMF, as it is in myelodysplastic syndromes. © 2009 Wiley-Liss, Inc. Source

Caramazza D.,Policlinico Universitario Of Palermo | Hussein K.,Mayo Medical School | Siragusa S.,Policlinico Universitario Of Palermo | Pardanani A.,Mayo Medical School | And 3 more authors.
European Journal of Haematology

Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype-phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL-negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplications (e.g. 1q12→1q32 in PV, 1q21-32→1q32-44 in post-PV MF or PMF), deletions (e.g. 1p13-36→pter in PV or PMF, 1q21 in PMF) and unbalanced translocations involving chromosome 6, such as der(6)t(1;6)(q21- 25;p21.3-23), and other partner chromosomes involving 1q10/1p11 and 1q21-25 breakpoints. Although occasionally seen in chronic phase MPN, unbalanced 1;7 translocations, e.g. der(1;7)(q10;p10), are usually seen in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and post-MPN AML/MDS. These observations suggest that certain chromosome 1 regions, especially 1q21-1q32 and 1p11-13, might harbor oncogenes or tumor suppressor genes that are pathogenetically relevant to both chronic and advanced phases of MPN. © 2009 John Wiley & Sons A/S. Source

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